Haterumalide NA is a recently isolated macrolide from an Okinawan sponge Ircinia sp. It was found to exhibit strong cytotoxicity against P388 leukemia cells. The goal of this research project is to develop a concise, modular, and efficient enantioselective synthesis of haterumalide NA. To achieve this synthesis, new methodology will be developed for the stereosetective formation of tri- and tetrasubstituted olefins. This novel process will be a two-step sequence consisting of the synthesis of substituted cycloalkenylsiloxanes from propargyl alcohols followed by metal-mediated coupling with an organohalide. The development of this synthesis will create sufficient quantities of haterumalide NA for further exploration of its biological activity. Furthermore, the novel methodology proposed and the flexible synthetic scheme will permit straightforward access to analogs of haterumalide NA that may lead to a structure activity profile and the discovery of new anticancer drugs.